Prognostic factors of second hematopoietic allogeneic stem cell transplantation among hematological malignancy patients relapsed after first hematopoietic stem cell transplantation: A single center study

Abstract

IntroductionWe aimed to evaluate prognostic factors of a second allogeneic stem cell transplantation (allo-HSCT2) among hematological malignancy patients who have relapsed after the first allo-HSCT(allo-HSCT1).MethodsWe retrospectively analyzed 199 hematological malignancy patients who received allo-HSCT2 as a salvage treatment post allo-HSCT1 relapse between November 2012 and October 2021.ResultsThe median age at allo-HSCT2 was 23 (range: 3-60) years. The median time to relapse after HSCT1 was 9 (range: 1-72) months. Prior to allo-HSCT2, patients had the following hematopoietic cell transplantation-comorbidity indexes (HCT-CI): 127 with a score of 0, 52 with a score of 1, and 20 with a score of 2 or greater. Fifty percent of patients received chimeric antigen receptor (CAR) T-cell therapy following HSCT1 relapse. Disease status was minimal residual disease (MRD)-negative complete remission (CR) among 119 patients, MRD-positive CR among 37 patients and non-remission (NR) for 43 patients prior to allo-HSCT2. Allo-HSCT2 was performed from a new donor in 194 patients (97.4%) and 134 patients (67.3%) received a graft with a new mismatched haplotype. The median follow-up time was 24 months (range: 6-98 months), and the 2-year OS and LFS were 43.8% ± 4.0% and 42.1% ± 4.1%, respectively. The 2-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) was 30.0%±4.8% and 38.5%±3.8%, respectively. Cox regression multivariate analysis showed that disease statusof MRD-negative CR, HCT-CI score of 0 prior to allo-HSCT2, and new mismatched haplotype donor were predictive factors of improved OS and LFS compared to patients without these characteristics. Based on these three favorable factors, we developed a predictive scoring system for patients who received allo-HSCT2. Patients with a prognostic score of 3 who had the three factors showed a superior 2-year OS of 63.3% ± 6.7% and LFS of 63.3% ± 6.7% and a lower CIR of 5.5% ± 3.1% than patients with a prognostic score of 0. Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 —disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT.ConclusionsAllo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 —disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT.

Risk factors and survival analysis of human leukocyte antigen loss in relapsed acute myeloid leukaemia/myelodysplastic syndrome patients after allogeneic haematopoietic stem cell transplantation

“…Despite the high transplant-related mortality rate of secondary transplantation, it still remains the only viable option with 2-year OS up to 43.8% and 5-year OS up to 25%. [28][29][30] According to the previous studies conducted by researchers from Europe and the United States, secondary transplantation with a different donor and/or conditioning intensity from the first HSCT did not bring survival benefit. 30,31 Our findings showed that the secondary transplantation significantly improve the OS in the HLA loss group, but the improvement of OS in the non-HLA loss group was not significant.…”

“…Despite the high transplant‐related mortality rate of secondary transplantation, it still remains the only viable option with 2‐year OS up to 43.8% and 5‐year OS up to 25% 28–30 . According to the previous studies conducted by researchers from Europe and the United States, secondary transplantation with a different donor and/or conditioning intensity from the first HSCT did not bring survival benefit 30,31 .…”

Analysis benefits of a second Allo-HSCT after CAR-T cell therapy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia who relapsed after transplant

“…Long-term follow-up data from EBMT showed that 120 ALL patients who relapsed after their first transplant received a second transplant with an expected 10-year OS of 5 ± 3%, LFS of 4 ± 2%, RI of 60 ± 5% and NRM of 36 ± 5% ( 27 ). A retrospective analysis of 199 second transplants of hematologic malignancy (48.2% B-ALL) from our center showed that achieving MRD-negative CR, HCT-CI score of 0 before allo-HSCT2, and utilizing a new mismatched haplotype donor were predictive factors of improved OS and LFS compared to patients without these characteristics in second transplant ( 28 ). The 2-year OS was 56.5% for the MRD-negative and 22.2% for the MRD-positive/NR groups, respectively ( 28 ).…”

“…A retrospective analysis of 199 second transplants of hematologic malignancy (48.2% B-ALL) from our center showed that achieving MRD-negative CR, HCT-CI score of 0 before allo-HSCT2, and utilizing a new mismatched haplotype donor were predictive factors of improved OS and LFS compared to patients without these characteristics in second transplant ( 28 ). The 2-year OS was 56.5% for the MRD-negative and 22.2% for the MRD-positive/NR groups, respectively ( 28 ). Consequently, achieving CR or even MRD-negative CR is crucial before undergoing a second transplant.…”

Influence of cyclosporine A trough level on acute graft versus host disease prophylaxis in pediatric allo- hematopoietic stem cell transplantation

“…In addition, Handgretinger [22] estimates that more than half of all HLA haplotype-mismatched transplants will be performed worldwide following similar protocols. Previous studies at our center demonstrated that conditioning regimens based on GIAC achieved favorable engraftment, OS, and an acceptable morbidity of GVHD among allo-HSCT patients [23][24][25][26][27][28][29].…”